The objective of this research is to answer the question: What are the characteristics of molecular flux across morphologically altered microvasculature of tumors and how are these characteristics influenced by induced blood flow? We believe that we will encounter differences in flux when compared with the normal microcirculation and our research is designed to identify the important parameters involved. The rationale for our plan is, in brief, based on evidence that 1) the vasculature and blood flow of tumors is known to be abnormal 2) flux of molecules from the vascular space to tumor thereby encounters special conditions. Our methodology involves: use of experimental mammary tumors in C3H mice. DMBA rats and human adenocarcinoma of the breast transplants in nude athymic mice. The microvasculature will be observed using a special nuclear medicine microscope which makes it possible to simultaneously monitor radioisotope activity and observe blood flow and morphology both in areas 60 microns in diameter in living microcirculation. 11C labelled cyclophosphamide, 18F-5 fluorouracil and 68 Gallium will be administered to these animals and the flux of the isotopes across normal and abnormal microvessesl will be correlated. We will show that the transfer of the radiolabeled chemotherapeutic agents occurs at a different rate across the altered endothelium of the microvasculature in mammary tumors as compared to normal endothelium in a resting mammary gland. The methodology is direct in concept. It is made possible through the use of a new device, the Nuclear Biology Microscope, which has been designed and tested by the applicants.